To the best of our knowledge, this work is the first study systematically assessing the impact of simultaneous fMRI scan on FDG-PET in human brain with an integrated PET/MR system. Our protocol is a self-control study design following the recommended clinical routine, where MR sequences were performed 30 to 40 minutes after the injection of 18F-FDG. It’s commonly considered that FDG-PET data acquired during this plateau phase of uptake curve mainly represents the neuronal activity occurred during the preceding early uptake phase. Thus, SUVr for plateau phase is supposed to be steady even when fMRI scan is synchronously performed. Our results found no difference in neither mean SUVr nor voxel-wise SUVr compared between MRI-on and MRI-off period, which supported this inference. However, obvious increase of Patlak Ki was detected in MRI-on period across the whole brain, including grey matter, white matter, cerebellum and eight specific functional networks. This unspecific global metabolic change reflects a short-term FDG uptake elevation due to the fMRI scan, but may not in favour of a neuronal origin, whose activation should mainly locate in grey matter regions. We assume that this phenomenon may due to other physiological inference, such as temperature-dependent acceleration of metabolic rates. Thus, with only minor amount of free FDG in blood pool available, fMRI scan in the steady state could only produce limited and unspecific effect on the trend of FDG elevation, which does not affect the calculation of SUVr value to statistical significance.
In the network-wise comparison, when treating fMRI scan as a stimulation task, the effected components were located in the default, auditory, visual and language networks, which were commonly regarded as “higher-order” cognitive networks. A previous study reported that 13 meaningful RSNs could be detected from FDG-PET data acquired 10 minutes to 30 minutes post-injection. Among them, seven networks could be detected by both modalities, including default mode, left central executive, primary and secondary visual, sensorimotor, cerebellar, and auditory networks . In our study, the “activated” networks induced by fMRI scan fundamentally located in these “dually” detected RSNs, which could be explained by changes of either cerebral blood flow or activity-dependent glucose consumption. As our data was acquired 30 minutes post-injection, the contribution of a blood flow signal change caused by the instant injection of FDG could be negligible. In this way, these “activations” observed in our ICA results should be regarded as comparable elevated glucose consumption, rather than increased cerebral blood flow or oxygen consumption.
In previous studies, the possible mechanism underlying neurometabolic coupling was explained by temporally synchronized cerebral blood flow and energy utilization, based on the theory that resting-state glucose and oxygen metabolism were closely linked . Strong coupling was found in default and visual networks, while weak correlation was found in limbic and somatomotor network . The highest correlation between rCMRGlu and fMRI metrics were achieved in ReHo, which was both detected by using integrated PET/MR or separated PET and MRI devices [3, 36, 37]. Other metrics, such as ALFF or DC, showed lower association with CMRGlu, maybe strongly affected by venous vasculature or other non-neuronal factors on signal amplitude . These differences could also be explained by the different physiological phenomena probed by each metric. ALFF contrast is only due to single voxel signal. ReHo could be considered as a measurement of short-range FC affected by neighbouring 27 voxels, while DC measures distant voxels weighted by long-range FC in the whole brain.
Our study reports a synthesis effect of MRI scan on quantitative PET in an integrated system. Among all possible factors, acoustic MRI noise resulting from echo-planar imaging (EPI) should be regarded as the main concern. This sequence is normally accompanied by a gradient-shifting noise with sound level greater than 100dB . Studies have focused on measuring how background acoustic noise influence the hemodynamic responses in auditory cortex and made efforts to spoil the interference . Reduced activation in the visual cortex was also reported, which may relate to attention modulation due to auditory-visual cross-modal neural interaction . Increased activation of working-memory network , as well as suppressed activation in the default-mode network and sensorimotor cortex [25, 26], were respectively discussed under the presence of BOLD-related noise. “Quieter” fMRI acquisition methods, such as sparse temporal sampling or interleaved silent steady state, could be applied to a less noisy background environment for BOLD-fMRI scan . In addition, MR-induced RF power deposition and the resulting effects on temperature-dependent metabolic rates could also influence FDG uptake, with maximum relative increases of 26% for uptake models based on metabolism . We speculate that these above factors synergistically influenced brain metabolism during the static phase of FDG uptake in our study.
This work was subject to several limitations. First, we adopted a blood-free approach to estimate the relative quantification of CMRGlu, which is more tolerable for a universal clinical routine. However, for a more precise design, absolute quantification of CMRGlu could be calculated by infusion of 18F-FDG and venous blood sampling . Second, methodologically, ICA and seed-based functional connectivity (sbFC) are two main approaches for statistical mapping of RSNs derived from FDG-PET. It’s been discussed that the choice of ICA or sbFC could influence the detectability of RSNs especially when sample size is limited . Future studies could retest and verify our results by different data analysis methods on the basis of a larger dataset.